Simplifi ed antibiotic regimens for treatment of clinicaludsevere infection in the outpatient setting when referral isudnot possible for young infants in Pakistan (Simplifi edudAntibiotic Therapy Trial SATT): a randomised, open-label,udequivalence trial

摘要

Background Parenteral antibiotic therapy for young infants (aged 0–59 days) with suspected sepsis is sometimes notudavailable or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings.udWe aimed to assess the equivalence of two simplifi ed antibiotic regimens, comprising fewer injections and oral ratherudthan parenteral administration, compared with a reference treatment for young infants with clinical severe infection.udMethods We undertook the Simplifi ed Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label,udequivalence trial in fi ve communities in Karachi, Pakistan. We enrolled young infants (aged 0–59 days) who eitherudpresented at a primary health-care clinic or were identifi ed by a community health worker with signs of clinical severeudinfection. We included infants who were not critically ill and whose family refused admission. We randomly assignedudinfants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oraludamoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillinudand gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome wasudtreatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimentaludtreatments as effi cacious as the reference if the upper bound of the 95% CI for the diff erence in treatment failure wasudless than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429.udFindings Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%)udwere enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in theudper-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillinudand gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and 817 (753 per protocol) wereudassigned procaine benzylpenicillin, gentamicin, and amoxicillin. Treatment failure within 7 days of enrolment wasudreported in 90 (12%) infants who received procaine benzylpenicillin and gentamicin (reference), 76 (10%) of those givenudamoxicillin and gentamicin (risk diff erence with reference –1·9, 95% CI –5·1 to 1·3), and 99 (13%) of those treated withudprocaine benzylpenicillin, gentamicin, and amoxicillin (risk diff erence with reference 1·1, –2·3 to 4·5).udInterpretation Two simplifi ed antibiotic regimens requiring fewer injections are equivalent to a reference treatmentudfor young infants with signs of clinical severe infection but without signs of critical illness. The use of these simplifi edudregimens has the potential to increase access to treatment for sick young infants who cannot be referred to hospital.